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Thromb Haemost 1998; 79(01): 69-73
DOI: 10.1055/s-0037-1614222
Review Article
Schattauer GmbH

Factor V Q506 Mutation (Activated Protein C Resistance) Associated with Reduced Intrapartum Blood Loss – a Possible Evolutionary Selection Mechanism

Pelle G. Lindqvist
1   The Department of Obstetrics and Gynaecology, University of Lund, University Hospital, Malmö, Sweden
,
Peter J. Svensson
2   The Department of Clinical Chemistry and Coagulation Research, University of Lund, University Hospital, Malmö, Sweden
,
Björn Dahlbäck
2   The Department of Clinical Chemistry and Coagulation Research, University of Lund, University Hospital, Malmö, Sweden
,
Karel Maršál
1   The Department of Obstetrics and Gynaecology, University of Lund, University Hospital, Malmö, Sweden
› Author Affiliations
Further Information

Publication History

Received 27 November 1996

Accepted after resubmission 10 September 1997

Publication Date:
08 December 2017 (online)

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Summary

Objectives. To ascertain whether relationship exists between the presence of APC resistance [a hypercoagulable state due to a mutation (R506Q) in the factor V gene] and the occurrence of pre-eclampsia (PE), intrauterine growth retardation (IUGR), and pregnancy bleeding complications. Design. A retrospective study. Subjects. A study group of 122 women with PE and/or IUGR during a recent pregnancy and a control group of 465 healthy pregnant women. Results. A significantly reduced risk of intrapartum bleeding complications in the APC-resistant subgroup as compared to the non-APC-resistant subgroup was suggested by reduced intrapartum blood loss, and pre- and postpartum haemoglobin measurements. The prevalence of APC resistance in the PE and IUGR subgroups did not differ significantly from that in the control group. Conclusion. The remarkably high prevalence of the potentially harmful factor V gene mutation in the general population may be the result of an evolutionary selection mechanism conferring such survival advantages as reduction in the risk of intrapartum bleeding on carriers of the FV:Q506 allele.

 

  • References

  • 1 Dahlbäck B, Stenflo J. A natural anticoagulant pathway: proteins c, s, c4b-binding protein and thrombomodulin. In: Haemostasis and thrombosis. Bloom A, Forbes C, Thomas D, and Tuddenham E. (eds) Churchill Livingstone; London: 1994. pp 671-98.
    Google Scholar
  • 2 Greer I. Haemostasis and thrombosis in pregnancy. In: Haemostasis and Thrombosis. Bloom A, Forbes C, Thomas D, and Tuddenham E. (eds) Churchill Livingstone; London: 1994. pp 987-1015.
    Google Scholar
  • 3 Sipes SL, Weiner CP. Venous thromboembolic disease in pregnancy. Semin Perinatol 1990; 14: 103-18.
    PubMedGoogle Scholar
  • 4 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
    CrossrefPubMedGoogle Scholar
  • 5 Dahlbäck B. Inherited thrombophilia: resistance to activated protein C as a pathogenic factor of venous thromboembolism. Blood 1995; 85: 607-14.
    PubMedGoogle Scholar
  • 6 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
    CrossrefPubMedGoogle Scholar
  • 7 Beauchamp NJ, Daly ME, Hampton KK, Cooper PC, Preston FE, Peake IR. High prevalence of a mutation in the factor V gene within the U.K. population: relationship to activated protein C resistance and familial thrombosis. Br J Haematol 1994; 344: 694-5.
    PubMedGoogle Scholar
  • 8 Emmerich J, Poirier O, Evans A, Marques Vidal P, Arveiler D, Luc G, Aiach M, Cambien F. Myocardial infarction, Arg 506 to Gln factor V mutation, and activated protein C resistance. Lancet 1995; 345: 321.
    CrossrefPubMedGoogle Scholar
  • 9 Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 1995; 332: 912-7.
    CrossrefPubMedGoogle Scholar
  • 10 Catto A, Carter A, Ireland H, Bayston TA, Philippou H, Barrett J, Lane DA, Grant PJ. Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke. Arterioscler Thromb Vasc Biol 1995; 15: 783-5.
    CrossrefPubMedGoogle Scholar
  • 11 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
    CrossrefPubMedGoogle Scholar
  • 12 Holm J, Zöller B, Berntorp E, Erhardt L, Dahlbäck B. Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries. Journal of internal Medicine 1996; 239: 221-6.
    CrossrefPubMedGoogle Scholar
  • 13 Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453-7.
    CrossrefPubMedGoogle Scholar
  • 14 Hellgren M, Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol 1995; 173: 210-3.
    CrossrefPubMedGoogle Scholar
  • 15 Redman CW. Current topic: pre-eclampsia and the placenta. Placenta 1991; 12: 301-8.
    CrossrefPubMedGoogle Scholar
  • 16 Dekker GA, de Vries JI, Doelitzsch PM, Huijgens PC, von Blomberg BM, Jakobs C, van Geijn HP. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol 1995; 173: 1042-8.
    CrossrefPubMedGoogle Scholar
  • 17 Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343: 1536-8.
    CrossrefPubMedGoogle Scholar
  • 18 International classification of diseases. ninth revision (ICD-9). World Health organisation; Geneva: 1976
    Google Scholar
  • 19 Marsál K, Persson PH, Larsen T, Lilja H, Selbing A, Sultan B. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr 1996; 85: 843-8.
    CrossrefPubMedGoogle Scholar
  • 20 Majerus PW. Human genetics. Bad blood by mutation. Nature 1994; 369: 14-5.
    CrossrefPubMedGoogle Scholar
  • 21 Dahlbäck B. Physiological anticoagulation. Resistance to activated protein C and venous thromboembolism. J Clin Invest 1994; 94: 923-7.
    CrossrefPubMedGoogle Scholar
  • 22 Hajjar KA. Factor V Leiden – an unselfish gene?. N Engl J Med 1994; 331: 1585-7.
    CrossrefPubMedGoogle Scholar
  • 23 Dobbie BM. An attempt to estimate the true rate of maternal mortality, sixteenth to eighteenth centuries. Med Hist 1982; 26: 79-80.
    CrossrefPubMedGoogle Scholar
  • 24 Högberg U. Maternal deaths in Sweden, 1971-1980. Acta Obstet Gynecol Scand 1986; 65: 161-7.
    CrossrefPubMedGoogle Scholar
  • 25 Zivelin A, Griffin JH, Xu X, Pabinger I, Samama M, Conard J, Brenner B, Eldor A, Seligsohn U. A single genetic origin for a common Caucasian risk factor for venous thrombosis. Blood 1997; 89: 397-402.
    PubMedGoogle Scholar
  • 26 Groube L. The impact of diseases upon the emergence of agriculture. In: The origins and spread of agriculture and pastoralism in Eurasia. Harris D. editor. UCL press; London: 1996. pp 101-129.
    Google Scholar
  • 27 Wiesenfeld SL. Sickle-cell trait in human biological and cultural evolution. Development of agriculture causing increased malaria is bound to gene-pool changes causing malaria reduction. Science 1967; 157: 1134-40.
    CrossrefPubMedGoogle Scholar
  • 28 Allison A, Phil D. Protection afforded by sickle-cell trait against subtertian malarial infection. BMJ 1954; 1: 290-4.
    CrossrefPubMedGoogle Scholar